Ion guide with orthogonal sampling

ABSTRACT

A mass spectrometer is disclosed comprising a RF ion guide wherein in a mode of operation a continuous, quasi-continuous or pulsed beam of ions is orthogonally sampled from the ion guide and wherein the continuous, quasi-continuous or pulsed beam of ions is not axially trapped or otherwise axially confined within the RF ion guide. The ion guide is maintained, in use, at a pressure selected from the group consisting of: (i) 0.0001-0.001 mbar; (ii) 0.001-0.01 mbar; (iii) 0.01-0.1 mbar; (iv) 0.1-1 mbar; (v) 1-10 mbar; (vi) 10-100 mbar; and (vii) &gt;100 mbar.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.14/004,529, filed Sep. 11, 2013, now U.S. Pat. No. 8,716,660 which isthe National Stage of International Application No. PCT/GB2012/050544filed 13 Mar. 2012 which claims priority from and the benefit of U.S.Provisional Patent Application Ser. No. 61/476,866 filed on 19 Apr. 2011and United Kingdom Patent Application No. 1104220.7 filed on 14 Mar.2011. The entire contents of these applications are incorporated hereinby reference.

BACKGROUND TO PRESENT INVENTION

The present invention relates to a mass spectrometer and a method ofmass spectrometry. The preferred embodiment relates to an ion guide andmethod of guiding ions.

Various separation techniques for separating ions are known and may bebroadly divided into two different types. A first type involvesperforming separation or filtering from a continuous stream of analyteions. A second type involves analyte ions being delivered in a focussedpulse or as a discontinuous stream of ions.

Devices or techniques which can separate or identify individualcomponents from a continuous stream of analyte ions include RFquadrupole mass filters, magnetic sector mass spectrometers,electrostatic analysers, UV and fluorescence spectrometers anddifferential ion mobility spectrometers.

Devices or techniques which require discontinuous delivery of analyteions to separate or identify individual components include gaschromatography, liquid chromatography, Time of Flight massspectrometers, ion mobility spectrometers, FTICR mass spectrometers andRF and electrostatic ion traps.

In general, for devices or techniques which require discontinuousdelivery of analyte ions a period of time must be allowed to elapsebetween each introduction of a pulse of analyte ions. Often this periodof time represents the entire time required to complete the analysis ofa prior pulse of analyte ions.

Considering techniques wherein analyte molecules are continuouslyionised to produce a continuous beam of ions, such as Electrosprayionisation, a narrow pulse of ions may be generated by gating a smallsection of the ion beam into the mass spectrometer. The analyticalperformance of the device is inversely proportional to the width in timeof the gated portion of the ion beam. For example, in IMS analysis atypical analysis time may be of the order of 10 ms and a gate width maybe of the order of 100 μs. If the remaining incoming ion beam is lostduring the 10 ms analytical time then the duty cycle for such a devicewill be of the order of 1%.

Several approaches have been developed to try to improve the duty cyclefor devices such as Ion Mobility Spectrometers (“IMS”). Ions may, forexample, be accumulated in an ion storage trap and the ion trap may beused to generate a pulse of ions for analysis. Ions arriving at the iontrap during the analysis time may be accumulated within the ion trapready for the next analysis period. This method has been used enablingduty cycles approaching 100% to be obtained for ion traps, IMS analysisand Time of Flight analysis.

However, efficient ion trapping with RF confining fields is difficult atpressures approaching atmospheric pressure and also at very lowpressures where ions do not lose kinetic energy rapidly due tocollisions with background gas molecules. Commercial atmosphericpressure IMS devices do not employ either RF ion traps or RF ion guides.

A second approach to the problem of poor duty cycle is multiplexingwherein ions are pulsed into a mass spectrometer at a frequency fasterthat the frequency imposed by the total analysis time of the device.This produces complex spectra which need to be de-convolved based onknowledge of the initial gating frequency or encoding pattern. Hadamardtransform Time of Flight is an example of this approach.

A third approach commonly employed for Time of Flight mass spectrometryis orthogonal extraction. A relatively large section of an ion beam isextracted orthogonally by application of a sudden voltage pulse. As theenergy spread of the beam in the orthogonal direction is relatively lowcompared with the axial direction, very high resolution time of flightanalysis can be realised with duty cycles of the order of 20%-40%.

For time of flight analysis orthogonal extraction of a continuous ionbeam is performed at very low pressures to minimise collisions withbackground gas which would otherwise degrade the performance of the Timeof Flight analyser and/or cause collisionally induced fragmentation.

It is desired to provide an improved mass spectrometer and method ofmass spectrometry.

SUMMARY OF THE INVENTION

According to an aspect of the present invention there is provided a massspectrometer comprising:

an RF ion guide comprising a plurality of electrodes wherein in a modeof operation a continuous, quasi-continuous or pulsed beam of ions isorthogonally sampled from the ion guide and wherein the continuous,quasi-continuous or pulsed beam of ions is not axially trapped orotherwise axially confined within the RF ion guide; and

a device arranged and adapted to maintain the ion guide at a pressureselected from the group consisting of: (i) 0.0001-0.001 mbar; (ii)0.001-0.01 mbar; (iii) 0.01-0.1 mbar; (iv) 0.1-1 mbar; (v) 1-10 mbar;(vi) 10-100 mbar; and (vii) >100 mbar.

Ions are confined within the RF ion guide by a radial pseudo-potentialwhich acts to confine ions in at least one radial direction within theion guide.

The beam of ions is preferably non-mass selectively sampled or otherwiseejected from the ion guide.

The mass spectrometer preferably further comprises a device arranged andadapted to apply a DC potential to at least some of the electrodes inorder to cause ions to be orthogonally sampled from the ion guidepreferably in a non-mass or non-mass to charge ratio selective manner.

According to a less preferred embodiment the mass spectrometer mayfurther comprise a device arranged and adapted to apply a (small) RFpotential in addition to the DC potential to at least some of theelectrodes in order to cause ions to be orthogonally sampled from theion guide.

The mass spectrometer may further comprise a device arranged and adaptedto urge ions along at least a portion, or substantially the whole of theaxial length of the ion guide. The device is preferably arranged andadapted either:

(i) to apply one or more transient DC voltages or potentials to at leastsome of the electrodes; and/or

(ii) to maintain a DC voltage gradient along at least a portion orsubstantially the whole of the axial length of the ion guide; and/or

(iii) to apply a RF voltage having three or more phases to at least someof the electrodes, wherein different phases of the RF voltage areapplied to different electrodes.

According to an embodiment ions may be pre-separated according to aphysico-chemical property prior to arriving at said ion guide and/orwhilst being transmitted through the ion guide.

According to an embodiment the physico-chemical property may comprisemass or mass to charge ratio. As a result, orthogonally sampling thebeam of ions has the effect of selecting ions having masses or mass tocharge ratios within a particular mass or mass to charge ratio range.

According to another embodiment the physico-chemical property maycomprise ion mobility or differential ion mobility. As a result,orthogonally sampling the beam of ions has the effect of selecting ionshaving ion mobilities or differential ion mobilities within a particularion mobility or differential ion mobility range.

The RF ion guide preferably comprises at least 6, 7, 8, 9, 10, 11, 12,13, 14, 15, 16, 17, 18, 19 or 20 electrodes. A RF voltage is preferablyapplied to the at least 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18,19 or 20 electrodes.

The ion guide is preferably maintained, in use, at a pressure such thatthe mean free path of ions within the ion guide is substantially lessthan the length of the ion guide.

The plurality of electrodes may comprise substantially planarelectrodes.

According to another embodiment the plurality of electrodes may compriserod or ring electrodes.

The continuous, quasi-continuous or pulsed beam of ions is preferablyorthogonally sampled so that a portion of the ion beam experiences anelectric field in a direction which is substantially orthogonal to theinitial direction of the ion beam.

The continuous, quasi-continuous or pulsed beam of ions is preferablyorthogonally sampled with a duty cycle selected from the groupconsisting of (i) <5%; (ii) 5-10%; (ill) 10-15%; (iv) 15-20%; (v)20-25%; (vi) 25-30%; (vii) 30-35%; (viii) 35-40%; (ix) 40-45%; (x)45-50%; (xi) 50-55%; (xii) 55-60%; (xiii) 60-65%; (xiv) 65-70%; (xv)70-75%; (xvi) 75-80%; (xvii) 80-85%; (xviii) 85-90%; (xix) 90-95%; and(xx) >95%.

The mass spectrometer preferably further comprises a device arranged andadapted to apply an AC or RF voltage to the electrodes in order toconfine ions within the ion guide in a first direction (y).

The mass spectrometer preferably further comprises a control system,wherein the control system is arranged and adapted in a first mode ofoperation to apply a DC voltage additionally to the electrodes in orderto confine ions within the ion guide in a second different direction(x). The second direction (x) is preferably orthogonal to the firstdirection (y).

The control system is preferably arranged and adapted to switch the ionguide to operate in a second mode of operation wherein ions areorthogonally sampled from a portion of the ion guide.

The mass spectrometer preferably further comprises an analyticalseparation device and wherein in the second mode of operation ions areorthogonally sampled from the ion guide and are transmitted to theanalytical separation device.

The analytical separation device preferably comprises: (i) a mass ormass to charge ratio separation device; (ii) an ion mobility separationdevice; or (iii) a differential ion mobility separation device.

The mass spectrometer may further comprise a reaction or collision cellwherein ions are orthogonally sampled from the ion guide and aretransmitted to the reaction or collision cell.

Ions within the ion guide may be separated with respect to their ionmobility, mass to charge ratio or differential ion mobility.

According to an embodiment the RF ion guide may comprise a quadrupolerod set, a hexapole rod set, an octopole rod set or a multipole rod sethaving ten or more rod electrodes.

According to an aspect of the present invention there is provided methodof mass spectrometry comprising:

providing a RF ion guide;

passing a continuous, quasi-continuous or pulsed beam of ions throughthe RF ion guide, wherein the continuous, quasi-continuous or pulsedbeam of ions is not axially trapped or otherwise axially confined withinthe RF ion guide;

orthogonally sampling the continuous, quasi-continuous or pulsed beam ofions; and

maintaining the ion guide at a pressure selected from the groupconsisting of; (i) 0.0001-0.001 mbar; (ii) 0.001-0.01 mbar; (iii)0.01-0.1 mbar; (iv) 0.1-1 mbar; (v) 1-10 mbar; (vi) 10-100 mbar; and(vii) >100 mbar.

According to an aspect of the present invention there is provided a massspectrometer comprising:

an RF ion guide comprising a plurality of electrodes wherein in a firstmode of operation a DC voltage is applied to the electrodes in order toconfine ions radially within the ion guide within a DC potential welland wherein in a second mode of operation the DC potential applied tothe electrodes is varied so that ions are orthogonally sampled from theion guide.

According to the preferred embodiment ions are not confined axiallywithin the ion guide during the first mode of operation.

According to an aspect of the present invention there is provided amethod of mass spectrometry comprising:

providing an RF ion guide comprising a plurality of electrodes;

applying a DC voltage to the electrodes in order to confine ionsradially within the ion guide within a DC potential well; and

varying the DC potential applied to the electrodes so that ions areorthogonally sampled from the ion guide.

According to the preferred embodiment ions are not confined axiallywithin the ion guide when ions are orthogonally sampled.

According to an aspect of the present invention there is provided a massspectrometer comprising:

an ion guide comprising a drift tube wherein in a mode of operation acontinuous, quasi-continuous or pulsed beam of ions is orthogonallysampled from the ion guide and wherein the continuous, quasi-continuousor pulsed beam of ions is not axially trapped or otherwise axiallyconfined within the ion guide; and

a device arranged and adapted to maintain the ion guide at a pressureselected from the group consisting of: (i) 0.0001-0.001 mbar; (ii)0.001-0.01 mbar; (iii) 0.01-0.1 mbar; (iv) 0.1-1 mbar; (v) 1-10 mbar;(vi) 10-100 mbar; and (vii) >100 mbar.

According to the preferred embodiment no RF voltage is applied to thedrift tube.

According to an aspect of the present invention there is provided amethod of mass spectrometry comprising:

providing an ion guide comprising a drift tube;

passing a continuous, quasi-continuous or pulsed beam of ions throughthe ion guide, wherein the continuous, quasi-continuous or pulsed beamof ions is not axially trapped or otherwise axially confined within theion guide;

orthogonally sampling the continuous, quasi-continuous or pulsed beam ofions; and

maintaining the ion guide at a pressure selected from the groupconsisting of: (i) 0.0001-0.001 mbar; (ii) 0.001-0.01 mbar; (iii)0.01-0.1 mbar; (iv) 0.1-1 mbar; (v) 1-10 mbar; (vi) 10-100 mbar; and(vii) >100 mbar.

According to the preferred embodiment no RF voltage is applied to thedrift tube.

The preferred embodiment preferably enables orthogonal sampling of afirst or primary ion beam at an elevated pressure. The pressure ispreferably such that the mean free path of an ion is substantially lessthan the length of the high pressure region.

The orthogonal sampling of the ion beam is preferably performed in anion guide wherein ions are confined within the ion guide by an RFvoltage.

However, less preferred embodiments are also contemplated whereinorthogonal sampling of an ion beam may be performed from a drift tubewith no RF confinement.

Ions are preferably orthogonally sampled into a further analyticalseparation device which may be arranged to separate ions either on thebasis of their mass to charge ratio or their ion mobility.

Ions may be orthogonally sampled into a reaction or collision cell.

The first or primary ion beam is preferably continuous or discontinuous.

The first or primary ion beam may be separated with respect to ionmobility or with respect to mass to charge ratio.

The first or primary ion beam may be separated or filtered with respectto differential ion mobility.

According to an embodiment the mass spectrometer may further comprise:

(a) an ion source selected from the group consisting of: (i) anElectrospray ionisation (“ESI”) ion source; (ii) an Atmospheric PressurePhoto Ionisation (“APPI”) ion source; (iii) an Atmospheric PressureChemical ionisation (“APCI”) ion source; (iv) a Matrix Assisted LaserDesorption Ionisation (“MALDI”) ion source; (v) a Laser Desorptionionisation (“LDI”) ion source; (vi) an Atmospheric Pressure Ionisation(“API”) ion source; (vii) a Desorption ionisation on Silicon (“DIOS”)ion source; (viii) an Electron impact (“EI”) ion source; (ix) a Chemicalionisation (“CI”) ion source; (x) a Field ionisation (“FI”) ion source;(xi) a Field Desorption (“FD”) ion source; (xii) an Inductively CoupledPlasma (“ICP”) ion source; (xiii) a Fast Atom Bombardment (“FAB”) ionsource; (xiv) a Liquid Secondary Ion Mass Spectrometry (“LSIMS”) ionsource; (xv) a Desorption Electrospray Ionisation (“DESI”) ion source;(xvi) a Nickel-63 radioactive ion source; (xvii) an Atmospheric PressureMatrix Assisted Laser Desorption Ionisation ion source; (xviii) aThermospray ion source; (xix) an Atmospheric Sampling Glow DischargeIonisation (“ASGDI”) ion source; and (xx) a Glow Discharge (“GD”) ionsource; and/or

(b) one or more continuous or pulsed ion sources; and/or

(c) one or more ion guides; and/or

(d) one or more ion mobility separation devices and/or one or more FieldAsymmetric Ion Mobility Spectrometer devices; and/or

(e) one or more ion traps or one or more ion trapping regions; and/or

(f) one or more collision, fragmentation or reaction cells selected fromthe group consisting of: (i) a Collisional Induced Dissociation (“CID”)fragmentation device; (ii) a Surface Induced Dissociation (“SID”)fragmentation device; (iii) an Electron Transfer Dissociation (“ETD”)fragmentation device; (iv) an Electron Capture Dissociation (“ECD”)fragmentation device; (v) an Electron Collision or Impact Dissociationfragmentation device; (vi) a Photo Induced Dissociation (“PID”)fragmentation device; (vii) a Laser induced Dissociation fragmentationdevice; (viii) an infrared radiation induced dissociation device; (ix)an ultraviolet radiation induced dissociation device; (x) anozzle-skimmer interface fragmentation device; (xi) an in-sourcefragmentation device; (xii) an in-source Collision Induced Dissociationfragmentation device; (xiii) a thermal or temperature sourcefragmentation device; (xiv) an electric field induced fragmentationdevice; (xv) a magnetic field induced fragmentation device; (xvi) anenzyme digestion or enzyme degradation fragmentation device; (xvii) anion-ion reaction fragmentation device; (xviii) an ion-molecule reactionfragmentation device; (xix) an ion-atom reaction fragmentation device;(xx) an ion-metastable ion reaction fragmentation device; (xxi) anion-metastable molecule reaction fragmentation device; (xxii) anion-metastable atom reaction fragmentation device; (xxiii) an ion-ionreaction device for reacting ions to form adduct or product ions; (xxiv)an ion-molecule reaction device for reacting ions to form adduct orproduct ions: (xxv) an ion-atom reaction device for reacting ions toform adduct or product ions; (xxvi) an ion-metastable ion reactiondevice for reacting ions to form adduct or product ions; (xxvii) anion-metastable molecule reaction device for reacting ions to form adductor product ions; (xxviii) an ion-metastable atom reaction device forreacting ions to form adduct or product ions; and (xxix) an ElectronIonisation Dissociation (“EID”) fragmentation device; and/or

(g) a mass analyser selected from the group consisting of: (i) aquadrupole mass analyser; (ii) a 2D or linear quadrupole mass analyser:(iii) a Paul or 3D quadrupole mass analyser; (iv) a Penning trap massanalyser; (v) an ion trap mass analyser; (vi) a magnetic sector massanalyser; (vii) Ion Cyclotron Resonance (“ICR”) mass analyser; (viii) aFourier Transform Ion Cyclotron Resonance (“FTICR”) mass analyser; (ix)an electrostatic or orbitrap mass analyser; (x) a Fourier Transformelectrostatic or orbitrap mass analyser; (xi) a Fourier Transform massanalyser; (xii) a Time of Flight mass analyser; (xiii) an orthogonalacceleration Time of Flight mass analyser; and (xiv) a linearacceleration Time of Flight mass analyser; and/or

(h) one or more energy analysers or electrostatic energy analysers;and/or

(i) one or more ion detectors; and/or

(j) one or more mass filters selected from the group consisting of: (i)a quadrupole mass filter; (ii) a 2D or linear quadrupole ion trap; (iii)a Paul or 3D quadrupole ion trap: (iv) a Penning ion trap; (v) an iontrap (vi) a magnetic sector mass filter; (vii) a Time of Flight massfilter; and (viii) a Wein filter; and/or

(k) a device or ion gate for pulsing ions; and/or

(l) a device for converting a substantially continuous ion beam into apulsed ion beam.

The mass spectrometer may further comprise either:

(i) a C-trap and an Orbitrap® mass analyser comprising an outerbarrel-like electrode and a coaxial inner spindle-like electrode,wherein in a first mode of operation ions are transmitted to the C-trapand are then injected into the Orbitrap® mass analyser and wherein in asecond mode of operation ions are transmitted to the C-trap and then toa collision cell or Electron Transfer Dissociation device wherein atleast some ions are fragmented into fragment ions, and wherein thefragment ions are then transmitted to the C-trap before being injectedinto the Orbitrap® mass analyser; and/or

(ii) a stacked ring ion guide comprising a plurality of electrodes eachhaving an aperture through which ions are transmitted in use and whereinthe spacing of the electrodes increases along the length of the ionpath, and wherein the apertures in the electrodes in an upstream sectionof the ion guide have a first diameter and wherein the apertures in theelectrodes in a downstream section of the ion guide have a seconddiameter which is smaller than the first diameter, and wherein oppositephases of an AC or RF voltage are applied, in use, to successiveelectrodes.

According to an embodiment one or more transient DC voltages orpotentials or the one or more DC voltage or potential waveforms may beapplied to the electrodes of the ion guide to create: (i) a potentialhill or barrier; (ii) a potential well; (iii) multiple potential hillsor barriers; (iv) multiple potential wells; (v) a combination of apotential hill or barrier and a potential well; or (vi) a combination ofmultiple potential hills or barriers and multiple potential wells.

The one or more transient DC voltage or potential waveforms preferablycomprise a repeating waveform or square wave.

An RF voltage is preferably applied to the electrodes of the ion guideand preferably has an amplitude selected from the group consisting of:(i) <50 V peak to peak; (ii) 50-100 V peak to peak; (iii) 100-150 V peakto peak; (iv) 150-200 V peak to peak; (v) 200-250 V peak to peak; (vi)250-300 V peak to peak; (vii) 300-350 V peak to peak; (viii) 350-400 Vpeak to peak; (ix) 400-450 V peak to peak; (x) 450-500 V peak to peak;(xi) 500-550 V peak to peak; (xxii) 550-600 V peak to peak; (xxiii)600-650 V peak to peak; (xxiv) 650-700 V peak to peak; (xxv) 700-750 Vpeak to peak; (xxvi) 750-800 V peak to peak; (xxvii) 800-850 V peak topeak; (xxviii) 850-900 V peak to peak; (xxix) 900-950 V peak to peak;(xxx) 950-1000 V peak to peak; and (xxxi) >1000 V peak to peak.

The RF voltage preferably has a frequency selected from the groupconsisting of: (i) <100 kHz; (ii) 100-200 kHz; (iii) 200-300 kHz; (iv)300-400 kHz; (v) 400-500 kHz; (vi) 0.5-1.0 MHz; (vii) 1.0-1.5 MHz;(viii) 1.5-2.0 MHz; (ix) 2.0-2.5 MHz; (x) 2.5-3.0 MHz; (xi) 3.0-3.5 MHz;(xii) 3.5-4.0 MHz; (xiii) 4.0-4.5 MHz (xiv) 4.5-5.0 MHz; (xv) 5.0-5.5MHz; (xvi) 5.5-6.0 MHz; (xvii) 6.0-6.5 MHz; (xviii) 6.5-7.0 MHz; (xix)7.0-7.5 MHz; (xx) 7.5-8.0 MHz; (xxi) 8.0-8.5 MHz; (xxii) 8.5-9.0 MHz;(xxiii) 9.0-9.5 MHz; (xxiv) 9.5-100 MHz; and (xxv) >10.0 MHz.

The ion guide is preferably maintained at a pressure selected from thegroup comprising: (i) >0.001 mbar; (ii) >0.01 mbar; (iii) >0.1 mbar;(iv) >1 mbar; (v) >10 mbar; (vi) >100 mbar; (vii) 0.001-0.01 mbar;(viii) 0.01-0.1 mbar; (ix) 0.1-1 mbar; (x) 1-10 mbar; and (xi) 10-100mbar.

BRIEF DESCRIPTION OF THE DRAWINGS

Various embodiments of the present invention will now be described, byway of example only, together with other arrangements given forillustrative purposes only and with reference to the accompanyingdrawings in which:

FIG. 1 shows a conventional arrangement wherein ions are gated into ahigh pressure analytical device;

FIG. 2 shows an ion guide according to a preferred embodiment of thepresent invention;

FIG. 3 shows a three dimensional representation of the ion guide shownin FIG. 2 according to an embodiment of the present invention;

FIG. 4A shows the form of a DC confining potential applied to theembodiment shown in FIG. 3 prior to causing at least some ions to besampled orthogonally and FIG. 4B shows the form of the DC potentialapplied to the ion guide shown in FIG. 3 in order to sample at leastsome ions orthogonally; and

FIG. 5 shows a simplified schematic diagram of an ion guide according toa preferred embodiment of the present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

A conventional mass spectrometer will first be described with referenceto FIG. 1. FIG. 1 shows a conventional mass spectrometer wherein aprimary ion beam 1 is prevented from entering a high pressure analyticaldevice 4 by an ion gate 2. The ion gate 2 is opened for a sufficientperiod of time so as to allow a narrow pulse of ions 3 to enter into theanalytical device 4. As ions traverse the analytical device 4 the ionsseparate temporally dependent upon either their ion mobility or theirmass to charge ratio. The ions are then transmitted to a furtherdownstream analyser, a fragmentation device or an ion detector 5 whichis arranged downstream of the analytical device 4.

FIG. 2 shows an ion guide according to a preferred embodiment of thepresent invention and FIG. 3 shows a corresponding three dimensionalview of the ion guide. According to the preferred embodiment acontinuous, quasi-continuous or pulsed beam of ions 1 is preferablyarranged to enter an RF ion guide 6 a,7,6 b. The ion guide 6 a,7,6 bpreferably comprises three sections 6 a,7,6 b and a fourth section 8.

According to the preferred embodiment the electrodes of a first ionguide section 6 a and the electrodes of a third ion guide section 6 bare preferably supplied with a RF potential wherein adjacent plates orelectrodes are preferably supplied with a RF voltage which is 180° outof phase. The applied RF potential results in a pseudo-potential forcewhich effectively contains or confines ions in the y (vertical)direction (see FIG. 3) within the first ion guide section 6 a and withinthe third ion guide section 6 b.

An intermediate second ion guide section 7 is preferably providedbetween the first ion guide section 6 a and the third ion guide section6 b. The second ion guide section 7 may be operated in two differentmodes of operation and may be operated either as an ion guide section oras an orthogonal acceleration region.

A fourth ion guide section 8 is preferably provided which may beoperated either as an ion guide to transmit ions to a further device oras an analytical separation region. The fourth ion guide section 8 ispreferably arranged adjacent the intermediate second ion guide section7, and preferably receives ions which have been orthogonally sampledfrom the intermediate second ion guide section 7.

In a transmission or ion guide mode of operation the electrodes of thefirst ion guide section 6 a, the electrodes of the second ion guidesection 7 and the electrodes of the third ion guide section 6 b arepreferably supplied with opposite phases of a RF voltage as describedabove so that ions are confined within the first, second and third ionguide sections 6 a,7,6 b in the y direction. In addition, a DC potentialis also preferably applied to the electrodes forming the first, secondand third ion guide sections 6 a,7,6 b so as to create a predominantlyDC confining force in the x (horizontal) direction. The form of theconfining DC well in the ion transmission or ion guiding mode is shownin FIG. 4A. In this mode of operation, ions preferably pass unhinderedthrough the first, second and third ion guiding regions 6 a,7,6 b of thedevice in the z (axial) direction. Ions may be urged in the z (axial)direction by the application of a DC or pseudo-potential field or byapplying a DC or pseudo-potential travelling wave to the electrodes ofthe ion guides 6 a,7,6 b.

FIG. 4B shows the DC field within the ion guide according to thepreferred embodiment during an orthogonal extraction mode of operation.In this mode of operation the second ion guide section 7 is preferablysupplied with a DC field which preferably acts to extract a portion ofthe ion beam in an orthogonal manner into the fourth ion guide section8. The fourth ion guide section 8 may be supplied with a static field ora travelling wave in order to urge ions along the axis of the fourth ionguide section 8.

Once a portion of the ion beam has exited the second ion guide section 7and has entered the fourth ion guide section 8 then the DC voltagesapplied to the electrodes of the first ion guide section 6 a, the secondion guide section 7 and the third ion guide section 6 b may be restoredto those shown in FIG. 4A. The ion beam may then be allowed to travelthrough the first and second ion guide sections 6 a,7 in order tore-populate the orthogonal extraction region of the second ion guidesection 7.

The confining RF and DC fields are preferably maintained in the fourthregion or ion guide section 8 during the re-population period.

Ions which have been extracted into the fourth ion guide section 8 maybe transmitted to another analytical device or to an ion detector. Thefourth ion guide section 8 may itself comprise an analytical device. Forexample, the fourth ion guide section 8 may comprise an ion mobilityseparation device. Ions which have been orthogonally injected into thefourth ion guide section 8 or ion mobility separation device may beurged through the fourth ion guide section 8 or ion mobilityspectrometer and through a drift gas by application of a DC field ortravelling wave to the electrodes forming the fourth ion guide section8. The time taken for ions to exit the fourth ion guide section or ionmobility separator device 8 is preferably related to the effectivecollision cross section of the analyte ions. As ions travel along thefourth ion guide section 8 they are preferably confined in the y(vertical) direction by a pseudo-potential force due to the applied RFpotential and in the z-direction by a DC force or potential well.

In the preferred embodiment the first ion guide section 6 a, the secondion guide section 7, the third ion guide section 6 b and the fourth ionguide section 8 may be maintained at effectively the same pressure.However, other embodiments are contemplated wherein the pressure and/orthe composition of the buffer gas in the first ion guide section 6 aand/or in the second ion guide section 7 and/or in the third ion guidesection 6 b and/or in the fourth ion guide section 8 may be different.

If it is assumed that the pressure and buffer gas composition areidentical in the first ion guide section 6 a, the second ion guidesection 7, the third ion guide section 6 b and the fourth ion guidesection 8 and that the field urging ions through the first ion guidesection 6 a, the second ion guide 7 and the third ion guide section 6 bin the axial or z-direction and in the x-direction of the fourth ionguide section 8 are identical, then analyte ions will travel throughthese regions at a velocity V_(d) related to their ion mobility:V _(d) ∝KE  (1)wherein V_(d) is the velocity of the ions, K is the mobility and E isthe electric field.

FIGS. 4A and 4B show a simplified schematic of the preferred device.With reference to FIG. 5, the length of a IMS separation region formedin the fourth ion guide section 8 may be defined as being L2. The lengthof the section of the ion beam which is orthogonally sampled from thesecond ion guide section 7 is L1. If the velocity of the ions in thecontinuous, quasi-continuous or pulsed beam is the same as the velocityof the ions in the ion mobility separation ion guide section 8, then themaximum duty cycle D₁ for a given analyte is given by:

$\begin{matrix}{D_{i} = {\frac{L\; 1}{L\; 2} \cdot \frac{K_{\min}}{K_{1}}}} & (2)\end{matrix}$wherein K_(min) is the lowest ion mobility associated with an analyteion present in the ion beam and K₁ is the ion mobility associated with aparticular analyte ion of interest.

Other modes of operation are contemplated which enable the duty cycle tobe improved. For example, the field in the axial or z direction E_(z)may be different to the field in the separation device or fourth ionguide section 8 in the x direction E_(x). If the field in the ion guidein the axial or z direction is arranged such that:

$\begin{matrix}{E_{z} = {\frac{L\; 1}{L\; 2} \cdot E_{x}}} & (3)\end{matrix}$then the maximum duty cycle D₂ is given by:

$\begin{matrix}{D_{2} = \frac{K_{\min}}{K}} & (4)\end{matrix}$

This results in a further improvement in duty cycle.

In another mode of operation a travelling wave or one or more transientDC voltages may be applied to the electrodes forming the first ion guidesection 6 a and/or the second ion guide section 7 and/or the third ionguide section 6 b in the axial or z direction and may be arranged toeffectively partition a continuous ion beam. All the ions may then betransported at the velocity of the travelling wave. The velocity of thetravelling wave may be arranged such that the extraction region L1becomes populated with all the analyte ions at the time of completion ofthe previous analytical scan of the fourth ion guide section 8 andimmediately prior to an orthogonal extraction pulse. As a result, it ispossible to achieve a duty cycle approaching 100%.

In another embodiment ions may be carried at constant velocity entrainedin a stream of buffer gas passing in the axial or z direction and may besampled orthogonally with high duty cycle.

It should be noted that these are maximum theoretical duty cyclecalculations. In practice the duty cycle may be reduced due to effectssuch as ion losses in the first ion guide section 6 a during the periodin which the extraction field is ON and ion losses during transfer ofions into the second device during orthogonal extraction.

An important aspect of the preferred embodiment is that gains in dutycycle may be made without compromising the performance of the analyticalseparation. The primary ion beam may be arranged to have a low spatialand energy spread in the direction of orthogonal sampling. In a systemwhere ions are gated into the analytical region, gains in duty cyclemade by increasing the gate time width will result in loss in analyticalperformance. Narrowing or focussing of the ion beam in the direction oforthogonal ejection is assisted in a RF or RF/DC confined ion guide bycollisional cooling of ions as a result of collisions with thebackground gas. Ions may achieve near thermal energy during progressthrough such ion guides and are confined to the minima of any confiningpotential well.

Although the preferred embodiment has been described using an RF ionguide, the same principle may be used to improve the duty cycle using aconventional drift tube with no RF confining field according to lesspreferred embodiments.

Other geometries of RF ion guide are contemplated including, forexample, RF ring stacks and RF rod sets with orthogonal extractionregions.

Further areas of orthogonal sampling may be provided in the first ionguide section 6 a and/or the second ion guide section 7 and/or the thirdion guide section 6 b.

Orthogonal sampling may be performed from the fourth ion guide section 8during analytical separation. For example, the fourth ion guide section8 may separate ions with respect to mass to charge ratio. A narrow massto charge ratio region may then be orthogonally sampled from the fourthion guide 8 into another analytical device to perform IMS separation ofthe ions within the sampled mass range. Thus IMS-MS or MS-IMS or IMS-IMSmay be performed.

The first ion guide section 6 a may itself be an analytical device suchas a mass filter or differential ion mobility filter.

Ions may be pulsed into the first ion guide section 6 a from a pulsedion source or from an ion trap and separation of the pulse of ions withrespect to mass to charge ratio or ion mobility may be performed withinthe first ion guide section 6 a. Multiple dimensions of separation maytherefore be performed.

In a mode of operation the orthogonal acceleration pulse may besynchronised to the release of ions from an ion trap resulting in 100%transmission for ions of a specific mass to charge ratio or ion mobilityvalue.

In addition, orthogonal sampling of the beam may be combined withmultiplexing approaches such that ions may be orthogonally sampled fromand/or injected into the first ion guide section 6 a at a higherfrequency than that imposed by the total analysis time of a furtheranalytical device or devices downstream of the fourth ion guidingsection 8. The resultant complex spectra produced may be de-convolvedbased on knowledge of the initial orthogonal sampling frequency orencoding pattern.

Ions which are not orthogonally accelerated from an ion guide may betransmitted thorough the ion guide to another downstream analyser ofdetector.

The orthogonal extraction pulse may be arranged to vary with time toallow a degree of spatial focussing of the sampled ion beam. This allowsthe resolution of a subsequent analytical device to be improved.

The axial force urging ions along each ion guide may be arranged to varyin amplitude or speed (in the case of a travelling wave) with time orwith position within the ion guide.

Many approaches which have been applied to orthogonal time of flightspectrometry to improve duty cycle are also applicable to orthogonalsampling within the higher pressure device according to an embodiment ofthe present invention as described above. For example, ions may bedelivered mass selectively into the first ion guide section 6 a over ashort period of time in sequence from high mass to charge ratio to lowmass to charge ratio. If the first ion guide section 6 a is itselfarranged to be a mass selective device wherein ions with low mass tocharge ratios have higher velocities through the device than ions withhigher mass to charge ratios, then the mass selective release of ionsfrom the ion trap may be matched to the mass selective separation withinthe ion guide such that ions of all mass to charge ratio values coincideat the orthogonal sampling region 7 at the same time. In this way 100%duty for ions of all mass to charge ratio values or a wide range of massto charge ratio values may be realised. Due to the correlation betweenmass to charge ratio and ion mobility for ions of the same charge state,a similar effect may be achieved by matching the release of ions from anion trap to the progress of ions through the first ion guide section 6 aacting as an ion mobility separator. In addition, ions may be releasedfrom the trap in order of mobility their arrival synchronised toorthogonal sampling to realise similar duty cycle improvements.

Alternatively, if ions are delivered mass selectively to the first ionguide section 6 a and this mass separation is retained as ions aretransported through this region, then repetitive orthogonal sampling ofthe ions may be synchronised to the ion injection such that ions fromeach mass to charge ratio range are effectively sampled with 100%efficiency.

This same effect may be achieved if ions are pulsed into the first ionguide section 6 a in a non-mass selective manner and the first ion guidesection 6 a is itself a mass or ion mobility separator. Multipleorthogonal sampling events, synchronised to the initial introduction ofions, may be performed. Each orthogonal sampling event results indifferent mass to charge ratio or mobility ranges being injected intothe downstream analytical device. The result is 100% efficiency for ionsof all mass to charge ratio or ion mobility values.

Although the present invention has been described with reference to thepreferred embodiments, it will be understood by those skilled in the artthat various changes in form and detail may be made without departingfrom the scope of the invention as set forth in the accompanying claims.

The invention claimed is:
 1. A mass spectrometer comprising: an RF ionguide comprising a plurality of electrodes wherein in a mode ofoperation ions are orthogonally sampled from said ion guide and whereinsaid ions are not axially trapped or otherwise axially confined withinsaid RF ion guide; a device arranged and adapted to apply an AC or RFvoltage to said electrodes in order to confine ions within said ionguide in a first direction (y); and a control system, wherein saidcontrol system is arranged and adapted in a first mode of operation toapply a DC voltage additionally to said electrodes in order to confineions within said ion guide in a second different direction (x); whereinsaid control system is arranged and adapted to switch said ion guide tooperate in a second mode of operation wherein ions are orthogonallysampled from a portion of said ion guide.
 2. A mass spectrometer asclaimed in claim 1, wherein said ions are non-mass selectively sampledor otherwise ejected from said ion guide.
 3. A mass spectrometer asclaimed in claim 1, further comprising a device arranged and adapted toapply a DC potential to at least some of said electrodes in order tocause ions to be orthogonally sampled from said ion guide.
 4. A massspectrometer as claimed in claim 3, further comprising a device arrangedand adapted to apply an RF potential in addition to said DC potential toat least some of said electrodes in order to cause ions to beorthogonally sampled from said ion guide.
 5. A mass spectrometer asclaimed in claim 1, further comprising a device arranged and adapted tourge ions along at least a portion or substantially all of an axiallength of said ion guide.
 6. A mass spectrometer as claimed in claim 5,wherein said device arranged and adapted to urge ions along at least aportion or substantially all of the axial length of said ion guide isarranged and adapted either: (i) to apply one or more transient DCvoltages or potentials to at least some of said electrodes; or (ii) tomaintain a DC voltage gradient along at least a portion or substantiallyall of the axial length of said ion guide; or (iii) to apply a RFvoltage having three or more phases to at least some of said electrodes,wherein different phases of said RF voltage are applied to differentelectrodes.
 7. A mass spectrometer as claimed in claim 1, wherein ionsare pre-separated according to a physico-chemical property prior toarriving at said ion guide or whilst being transmitted through said ionguide.
 8. A mass spectrometer as claimed in claim 7, wherein saidphysico-chemical property comprises mass or mass to charge ratio.
 9. Amass spectrometer as claimed in claim 8, wherein orthogonally samplingsaid ions has the effect of selecting ions having masses or mass tocharge ratios within a particular mass or mass to charge ratio range.10. A mass spectrometer as claimed in claim 7, wherein saidphysico-chemical property comprises ion mobility or differential ionmobility.
 11. A mass spectrometer as claimed in claim 10, whereinorthogonally sampling said ions has the effect of selecting ions havingion mobilities or differential ion mobilities within a particular ionmobility or differential ion mobility range.
 12. A mass spectrometer asclaimed in claim 1, wherein said RF ion guide comprises at least 6, 7,8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 electrodes, andwherein a RF voltage is applied, in use, to said at least 6, 7, 8, 9,10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 electrodes.
 13. A massspectrometer as claimed in claim 1, wherein said ion guide ismaintained, in use, at a pressure such that a mean free path of ionswithin said ion guide is substantially less than the length of said ionguide.
 14. A mass spectrometer as claimed in claim 1, wherein saidplurality of electrodes comprise substantially planar electrodes.
 15. Amass spectrometer as claimed in claim 1, wherein said plurality ofelectrodes comprise rod or ring electrodes.
 16. A mass spectrometer asclaimed in claim 1, wherein said ions are orthogonally sampled as an ionbeam so that a portion of said ion beam experiences an electric field ina direction which is substantially orthogonal to an initial direction ofsaid ion beam.
 17. A mass spectrometer as claimed in claim 1, whereinions are orthogonally sampled with a duty cycle selected from the groupconsisting of: (i) <5%; (ii) 5-10%; (iii) 10-15%; (iv) 15-20%; (v)20-25%; (vi) 25-30%; (vii) 30-35%; (viii) 35-40%; (ix) 40-45%; (x)45-50%; and (xi) 50-55%; (xii) 55-60%; (xiii) 60-65%; (xiv) 65-70%; (xv)70-75%; (xvi) 75-80%; (xvii) 80-85%; (xviii) 85-90%; (xix) 90-95%; and(xx) >95%.
 18. A mass spectrometer as claimed in claim 1, furthercomprising a device arranged and adapted to maintain the ion guide at apressure selected from the group consisting of: (i) 0.0001-0.001 mbar;(ii) 0.001-0.01 mbar; (iii) 0.01-0.1 mbar; (iv) 0.1-1 mbar; (v) 1-10mbar; (vi) 10-100 mbar; and (vii) >100 mbar.
 19. A mass spectrometer asclaimed in claim 1, further comprising an analytical separation deviceand wherein in a second mode of operation ions are orthogonally sampledfrom said ion guide and are transmitted to said analytical separationdevice.
 20. A mass spectrometer as claimed in claim 19, wherein saidanalytical separation device comprises: (i) a mass or mass to chargeratio separation device; (ii) an ion mobility separation device; or(iii) a differential ion mobility separation device.
 21. A massspectrometer as claimed in claim 1, further comprising a reaction orcollision cell and wherein ions are orthogonally sampled from said ionguide and are transmitted to said reaction or collision cell.
 22. A massspectrometer as claimed in claim 1, wherein ions within said ion guideare separated with respect to their ion mobility, mass to charge ratioor differential ion mobility.
 23. A mass spectrometer as claimed inclaim 1, wherein said RF ion guide comprises a quadrupole rod set, ahexapole rod set, an octopole rod set or a multipole rod set having tenor more rod electrodes.
 24. A method of mass spectrometry comprising:providing an RF ion guide comprising a plurality of electrodes; passingions through said RF ion guide, wherein said ions are not axiallytrapped or otherwise axially confined within said RF ion guide; applyingan AC or RF voltage to said electrodes in order to confine ions withinsaid RF ion guide in a first direction (y); applying in a first mode ofoperation a DC voltage additionally to said electrodes in order toconfine ions within said RF ion guide in a second different direction(x); and orthogonally sampling said ions from a portion of said RF ionguide in a second mode of operation.